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Ceramide and Sphingosine Regulation of Myelinogenesis: Targeting Serine Palmitoyltransferase Using microRNA in Multiple Sclerosis

1
Department of Neuroscience and Regenerative Medicine, Augusta University, 1120 15th Street, Augusta, GA 30912, USA
2
Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC 29209, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(20), 5031; https://doi.org/10.3390/ijms20205031
Received: 29 August 2019 / Revised: 30 September 2019 / Accepted: 9 October 2019 / Published: 11 October 2019
(This article belongs to the Special Issue Sphingolipids: Metabolic Functions and Disorders)
Ceramide and sphingosine display a unique profile during brain development, indicating their critical role in myelinogenesis. Employing advanced technology such as gas chromatography–mass spectrometry, high performance liquid chromatography, and immunocytochemistry, along with cell culture and molecular biology, we have found an accumulation of sphingosine in brain tissues of patients with multiple sclerosis (MS) and in the spinal cord of rats induced with experimental autoimmune encephalomyelitis. The elevated sphingosine leads to oligodendrocyte death and fosters demyelination. Ceramide elevation by serine palmitoyltransferse (SPT) activation was the primary source of the sphingosine elevation as myriocin, an inhibitor of SPT, prevented sphingosine elevation and protected oligodendrocytes. Supporting this view, fingolimod, a drug used for MS therapy, reduced ceramide generation, thus offering partial protection to oligodendrocytes. Sphingolipid synthesis and degradation in normal development is regulated by a series of microRNAs (miRNAs), and hence, accumulation of sphingosine in MS may be prevented by employing miRNA technology. This review will discuss the current knowledge of ceramide and sphingosine metabolism (synthesis and breakdown), and how their biosynthesis can be regulated by miRNA, which can be used as a therapeutic approach for MS. View Full-Text
Keywords: ceramide; development; microRNA; multiple sclerosis; MS therapy; oligodendrocytes protection; serine palmitoyltransferase; sphingosine ceramide; development; microRNA; multiple sclerosis; MS therapy; oligodendrocytes protection; serine palmitoyltransferase; sphingosine
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Dasgupta, S.; Ray, S.K. Ceramide and Sphingosine Regulation of Myelinogenesis: Targeting Serine Palmitoyltransferase Using microRNA in Multiple Sclerosis. Int. J. Mol. Sci. 2019, 20, 5031.

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